@jgt7771
I really wish I knew how to answer that as I am still experimenting myself. I personally think that you'll get a medium-difficulty game (thus not as interesting for the masochist club of AH veterans) if you play with 4 Investigators and the rules for 3 boards (count as -2 investigators, 1 more gate need be open for ancient one's appearance). The ground is already coverable for 4 investigators, and, quite frankly, there are too few monsters on the board with the 3-board rules.
I don't wish to be presumptuous, but I think a winnable, but challenging game can be played with 4 investigators and only using the +1 to the open gates limit for the ancient one. However, I base this off of only 1 game I played with all of the official rules+expansions and 4 investigators, and 2 games with 2 investigators with just Innsmouth (which had the usual difficulty of my 2 investigator games with all expansions minus black goat and innsmouth horror that I've had so far).
So in other words: *shrug*
Sorry that I can't be of more help.